Letrozole in Tubal Ectopic Pregnancy
Primary Purpose
Tubal Pregnancy
Status
Recruiting
Phase
Phase 3
Locations
Hong Kong
Study Type
Interventional
Intervention
Placebos
Letrozole tablets
Sponsored by
About this trial
This is an interventional treatment trial for Tubal Pregnancy focused on measuring Tubal ectopic pregnancy, Methotrexate, Letrozole
Eligibility Criteria
Inclusion Criteria:
- Tubal ectopic pregnancy suggested by presence of a heterogenous adnexal mass with suboptimal rise of hCG i.e. <= 63% rise over 48 hours
- hCG level <= 5000 IU/l
- Absence of fetal heart pulsation
- Mean diameter of adnexal mass <= 3.5cm
- Haemodynamically stable
- No significant abdominal pain
Exclusion Criteria:
- Presence of significant amount of free fluid in pelvis
- Allergic to MTX
- Deranged liver function test (AST/ ALT or GGT >= 2 upper limit of normal)
- Deranged renal function test (eGFR <= 45ml/min)
- Heterotopic pregnancies
Sites / Locations
- Department of Obstetrics and Gynaecology, Queen Mary HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Letrozole
Placebo
Arm Description
Participants will be given letrozole 10mg daily for one week after standard medical management for tubal ectopic pregnancy by methotrexate injection. Subsequently they will receive the standard management for medical management of tubal ectopic prengnacies.
Participants will be given identical looking placebo for one week and receive the same standard management for medical management of tubal ectopic pregnancies.
Outcomes
Primary Outcome Measures
Treatment success
Proportion of women with treatment success defined as normalization of serum hCG level <10IU/L without additional medical or surgical intervention
Secondary Outcome Measures
hCG normalization duration
Duration of time until hCG normalization measured in days
Number of participants experienced side effects
Side effects after letrozole
Duration of hospitalization
Duration of hospitalization
Participant satisfaction: proportion of women who would recommend this treatment to a friend
Treatment satisfaction measured as proportion of women who would recommend this treatment to a friend
Full Information
NCT ID
NCT04341545
First Posted
April 7, 2020
Last Updated
April 6, 2023
Sponsor
Queen Mary Hospital, Hong Kong
Collaborators
Kwong Wah Hospital, Princess Margaret Hospital, Hong Kong, Pamela Youde Nethersole Eastern Hospital, Hong Kong, Queen Elizabeth Hospital, Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT04341545
Brief Title
Letrozole in Tubal Ectopic Pregnancy
Official Title
Randomized Controlled Trial on Use of Letrozole in the Medical Management of Tubal Ectopic Pregnancies
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2020 (Actual)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Queen Mary Hospital, Hong Kong
Collaborators
Kwong Wah Hospital, Princess Margaret Hospital, Hong Kong, Pamela Youde Nethersole Eastern Hospital, Hong Kong, Queen Elizabeth Hospital, Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multi-centred randomized controlled trial on the addition of letrozole in the medical management of tubal ectopic pregnancies.
Tubal ectopic pregnancies are abnormal pregnancies in the Fallopian tube, rather than in the womb. They occurred in around 1-2% of all pregnancies. Methotrexate (MTX) given by the intramuscular route i.e. systemic, a commonly used drug for cancer , was a widely used alternative for management for unruptured tubal ectopic pregnancies and was recommended as first line treatment for selected women.
Letrozole, aromatase inhibitor, can suppose oestradiol level. Combination of letrozole with misprostol has shown to improve the complete abortion rate in miscarriage. As a result, addition of letrozole may cause a higher success rate in the medical treatment of ectopic pregnancy.
As the evidence of combination of MTX and letrozole in tubal ectopic pregnancies is not available, the objective of the present study is to evaluate the efficacy of combination of MTX and letrozole compared to MTX alone in women with tubal ectopic pregnancies.
Detailed Description
Tubal ectopic pregnancies occur in around 1-2% of all pregnancies. Traditionally, surgery with salpingectomy was the mainstay of treatment; however, it comes with anaesthetic and operatives risks in addition to an increased cost for operative procedures. In recent years, systemic methotrexate (MTX), a dihydrofolate reductase inhibitor, has been a widely used alternative for management for unruptured tubal ectopic pregnancies. The success rate of systemic MTX at a doses of 50mg/m2 body surface area is around 70% which ranges from 65 to 95%, depending greatly on the level of human chorionic gonadotrophin (hCG), the size of adnexal mass and presence of fetal heart pulsation.
Use of systemic MTX as the first-line management has been proposed for women with unruptured ectopic pregnancy where the adnexal mass is smaller than 35mm, serum hCG level is less than 5000 IU/l and fetal heartbeat is absent.
Letrozole is a third generation non-steroidal reversible aromatase inhibitor. It can suppress oestradiol level up to 95% to 99% after administration according to pharmacodynamics and pharmacokinetics studies. Oestrogen is important in the support of early pregnancy, other than progesterone with well-known pivotal effect on the maintenance of early pregnancy.
Animal studies showed the combination of mifepristone and letrozole worked synergistically and induced almost 100% termination of pregnancies in rats. Letrozole induced 50% miscarriage rate in pregnant baboons. Letrozole combined with vaginal misoprostol regimen was associated with a higher complete abortion rate than misoprostol alone in pregnancies up to 63 days.
The use of letrozole in ectopic pregnancy has never been explored. It is hypothesized that letrozole can suppress serum oestradiol level, which in turn, may cause failure of pregnancy in ectopic pregnancy. The aim of this study is to investigate the clinical effectiveness of letrozole in addition to MTX in the medical treatment of ectopic pregnancy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tubal Pregnancy
Keywords
Tubal ectopic pregnancy, Methotrexate, Letrozole
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized into either receive letrozole or placebo capsules.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The identical looking placebo will be given. A computer generated sequence will be created. The sequence will be sealed in consecutively concealed opaque envelopes. Both the participant/ care provider/ investigator and outcomes assessor will blinded to the group assigned.
Allocation
Randomized
Enrollment
214 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Letrozole
Arm Type
Experimental
Arm Description
Participants will be given letrozole 10mg daily for one week after standard medical management for tubal ectopic pregnancy by methotrexate injection. Subsequently they will receive the standard management for medical management of tubal ectopic prengnacies.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be given identical looking placebo for one week and receive the same standard management for medical management of tubal ectopic pregnancies.
Intervention Type
Other
Intervention Name(s)
Placebos
Intervention Description
Placebo 4 tablets a day for one week.
Intervention Type
Drug
Intervention Name(s)
Letrozole tablets
Other Intervention Name(s)
Letrozole
Intervention Description
Letrozole 10mg daily for one week.
Primary Outcome Measure Information:
Title
Treatment success
Description
Proportion of women with treatment success defined as normalization of serum hCG level <10IU/L without additional medical or surgical intervention
Time Frame
2 months
Secondary Outcome Measure Information:
Title
hCG normalization duration
Description
Duration of time until hCG normalization measured in days
Time Frame
2 months
Title
Number of participants experienced side effects
Description
Side effects after letrozole
Time Frame
2 months
Title
Duration of hospitalization
Description
Duration of hospitalization
Time Frame
2 months
Title
Participant satisfaction: proportion of women who would recommend this treatment to a friend
Description
Treatment satisfaction measured as proportion of women who would recommend this treatment to a friend
Time Frame
2 months
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Ectopic pregnancies studied
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Presence of heterogenous adnexal mass on USG suggestive of tubal ectopic pregnancy with hCG level >=1500 IU/L and <= 5000 IU/L
Absence of fetal heart pulsation
Mean diameter of adnexal mass <= 3.5cm
Haemodynamically stable
No significant abdominal pain
Exclusion Criteria:
Presence of significant amount of free fluid in pelvis
Allergic to MTX
Deranged liver function test (AST/ ALT or GGT >= 2 upper limit of normal)
Deranged renal function test (eGFR <= 45ml/min)
Heterotopic pregnancies
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Evelyn Wong, MBBS
Phone
22554517
Email
evelynwong.ew@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ernest H.Y. Ng, MD
Organizational Affiliation
The University of Hong Kong
Official's Role
Study Director
Facility Information:
Facility Name
Department of Obstetrics and Gynaecology, Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Chan, Prof
Phone
22554647
Email
kklchan@hku.hk
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Other researchers may contact the chief investigator for the request of individual participant data.
Citations:
PubMed Identifier
28620520
Citation
Panelli DM, Phillips CH, Brady PC. Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review. Fertil Res Pract. 2015 Oct 15;1:15. doi: 10.1186/s40738-015-0008-z. eCollection 2015.
Results Reference
background
PubMed Identifier
27813249
Citation
Diagnosis and Management of Ectopic Pregnancy: Green-top Guideline No. 21. BJOG. 2016 Dec;123(13):e15-e55. doi: 10.1111/1471-0528.14189. Epub 2016 Nov 3. No abstract available. Erratum In: BJOG. 2017 Dec;124(13):e314.
Results Reference
background
PubMed Identifier
27940397
Citation
Odejinmi F, Huff KO, Oliver R. Individualisation of intervention for tubal ectopic pregnancy: historical perspectives and the modern evidence based management of ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:69-75. doi: 10.1016/j.ejogrb.2016.10.037. Epub 2016 Oct 29.
Results Reference
background
Citation
National Collaborating Centre for Ws, Children's H. National Institute for Health and Clinical Excellence: Guidance. Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. London: Rcog National Collaborating Centre for Women's and Children's Health.; 2012.
Results Reference
background
PubMed Identifier
14668001
Citation
Shi L, Shi SQ, Given RL, von Hertzen H, Garfield RE. Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy. Steroids. 2003 Nov;68(10-13):1077-84. doi: 10.1016/j.steroids.2003.09.002.
Results Reference
background
PubMed Identifier
10694348
Citation
Albrecht ED, Aberdeen GW, Pepe GJ. The role of estrogen in the maintenance of primate pregnancy. Am J Obstet Gynecol. 2000 Feb;182(2):432-8. doi: 10.1016/s0002-9378(00)70235-3.
Results Reference
background
PubMed Identifier
21252745
Citation
Lee VCY, Ng EHY, Yeung WSB, Ho PC. Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. Obstet Gynecol. 2011 Feb;117(2 Pt 1):317-323. doi: 10.1097/AOG.0b013e3182073fbf.
Results Reference
background
PubMed Identifier
21134505
Citation
Lee VC, Tang OS, Ng EH, Yeung WS, Ho PC. A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days. Contraception. 2011 Jan;83(1):62-7. doi: 10.1016/j.contraception.2010.05.014. Epub 2010 Jun 23.
Results Reference
background
Learn more about this trial
Letrozole in Tubal Ectopic Pregnancy
We'll reach out to this number within 24 hrs